Exercise effects on DNA methylation in EVL, CDKN2A (p14, ARF), and ESR1 in colon tissue from healthy men and women.

Physical activity reduces risk of colon cancer persons by 20-30%. Aberrant methylation patterns are common epigenetic alterations in colorectal adenomas and cancers, and play a role in cancer initiation and progression. Alterations have been identified in normal colon tissue potentially representing a "field cancerization" process, where the normal colon is primed for carcinogenesis. Here, we investigate methylation patterns in three genes -Ena/VASP-like (EVL), (CDKN2A (p14, ARF)), and Estrogen Receptor-1 (ESR1)-in normal colon tissue collected at baseline and 12-months from 202 sedentary men and women, 40-75 years, enrolled in a randomized controlled trial testing an exercise intervention vs. control (http://clinicaltrials.gov/show/NCT00668161). Participants were randomized to moderate-to-vigorous intensity exercise, 60 minutes/day, 6 days/week for 12 months, or usual lifestyle. Sigmoid colon biopsies were obtained at baseline and 12-months, DNA extracted, and bisulphite converted. Droplet digital methylation-specific PCR was performed for EVL, p14ARF, and ESR1. Generalized estimating equations modification of linear regression were used to model relationships between intervention effects and candidate gene methylation levels, adjusting for possible confounders.There were no statistically significant differences between methylation patterns at 12-months between exercisers and controls. ESR1 methylation patterns differed by sex: women -10.58% (exercisers) +11.10% (controls); men +5.54% (exercisers), -8.16% (controls); (P=0.05), adjusting for BMI and age. There were no statistically significant changes in methylation patterns in any gene stratified by change in VO2max, or by minutes/week of exercise.While no statistically significant differences were found in gene methylation patterns comparing exercises vs. controls, 12-month exercise effects on ESR1 methylation differed by sex, warranting further study.